Described herein are CRISPR/Cas9 constructs designed for the C-terminal truncation of human amyloid precursor protein (APP) as well as methods of making and using such a construct. A Cas9 nuclease/gRNA ribonucleoprotein directs cleavage of an APP gene to provide a C-terminal truncated APP having a length of 659, 670, 676, or 686 amino acids, relative to the human or mouse APP sequence.

Provided are nucleic acid constructs and systems which comprise (i) a first nucleic acid construct encoding a toxin operatively linked to a first promoter and at least one cancer-associated signaling responsive enhancer element; and (ii) a second nucleic acid construct encoding an anti-toxin operatively linked to a second promoter, the second promoter being stronger than the first promoter. Also provided are pharmaceutical compositions comprising same and methods of using same for treating cancer.

The present invention relates to a lipid vesicle carrying a nucleic acid molecule for use as a medicament, wherein the lipid vesicle has a hydrodynamic diameter D.sub.h of less than 300 nm. The lipid vesicle is for oral administration, and the nucleic acid molecule is delivered to one or more of the target tissues selected from the group consisting of the central nervous system, spleen, gastrointestinal tract, liver and T-cells.

Disclosed herein, in certain embodiments, are recombinant Arc and endogenous Gag polypeptides, and methods of using recombinant Arc and endogenous Gag polypeptides.

Disclosed herein, in certain embodiments, are recombinant Arc and endogenous Gag polypeptides, and methods of using recombinant Arc and endogenous Gag polypeptides.

Disclosed herein are compositions and methods for modulating the production of a protein in a target cell. The compositions and methods disclosed herein are capable of ameliorating diseases associated with protein or enzyme deficiencies.

The present disclosure provides infectious recombinant adeno-associated virus (rAAV) virions that comprise a variant capsid protein and a heterologous nucleic acid. The present disclosure further provides the variant adeno-associated virus (AAV) capsid proteins (and/or a nucleic acid encoding the variant AAV capsid proteins), which confer to an infectious rAAV virion an increased resistance to human AAV neutralizing antibodies. The present disclosure further provides host cells comprising an infectious rAAV virion and/or a nucleic acid encoding a subject variant AAV capsid protein. The present disclosure further provides methods of delivering a heterologous nucleic acid to a target cell where the target cell is contacted with a subject infectious rAAV virion. The present disclosure further provides methods of delivering a gene product to an individual, the methods generally involving administering an effective amount of a subject rAAV virion to an individual in need thereof.

The present invention relates to a novel ionizable lipid and a lipid nanoparticle composition using same, wherein it has been identified that the lipid nanoparticle composed of the novel ionizable lipid exhibits an excellent rate of gene encapsulation efficiency and of gene delivery efficacy in in vitro/in vivo system and, simultaneously, exhibits an excellent rate of gene delivery efficacy even in serum-free environments, and thus the present invention can be effectively used as a composition for drug delivery.

Compositions for improved gene editing and methods of use thereof are disclosed. In a preferred method, gene editing involves use of a cell-penetrating anti-DNA antibody, such as 3E10, as a potentiating agent to enhance gene editing by nucleases and triplex forming oligonucleotides. Genomic modification occurs at a higher frequency when cells are contacted with the potentiating agent and nuclease or triplex forming oligonucleotide, as compared to the absence of the potentiating agent. The methods are suitable for both ex vivo and in vivo approaches to gene editing and are useful for treating a subject with a genetic disease or disorder. Nanoparticle compositions for intracellular delivery of the gene editing compositions are provided and are particularly advantageous for use with in vivo applications.

Compositions for enhanced gene editing and methods of use thereof are. The composition contains a cell-penetrating antibody and a donor oligonucleotide containing a sequence that can correct a mutation in a cell's genome. Preferably, the composition does not contain a nuclease, PNA, or nanoparticle. The compositions are used to modify the genome of a cell by contacting the cell with an effective amount of the composition. Genomic modification occurs at a higher frequency both ex vivo and in vivo, when cells are contacted with the cell-penetrating antibody and donor oligonucleotide as compared to the absence of the cell-penetrating antibody.